Crystal structure of the human ATP-dependent splicing and export factor UAP56.
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Shi H, Cordin O, Minder CM, Linder P, Xu RM
Crystal structure of the human ATP-dependent splicing and export factor UAP56.
Proc Natl Acad Sci U S A. 2004 Dec 21;101(51):17628-33. Epub 2004 Dec 7.
- PubMed ID
- 15585580 [ View in PubMed]
- Abstract
Pre-mRNA splicing requires the function of a number of RNA-dependent ATPases/helicases, yet no three-dimensional structure of any spliceosomal ATPases/helicases is known. The highly conserved DECD-box protein UAP56/Sub2 is an essential splicing factor that is also important for mRNA export. The expected ATPase/helicase activity appears to be essential for the UAP56/Sub2 functions. Here, we show that purified human UAP56 is an active RNA-dependent ATPase, and we also report the crystal structures of UAP56 alone and in complex with ADP, as well as a DECD to DEAD mutant. The structures reveal a unique spatial arrangement of the two conserved helicase domains, and ADP-binding induces significant conformational changes of key residues in the ATP-binding pocket. Our structural analyses suggest a specific protein-RNA displacement model of UAP56/Sub2. The detailed structural information provides important mechanistic insights into the splicing function of UAP56/Sub2. The structures also will be useful for the analysis of other spliceosomal DExD-box ATPases/helicases.